Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions

Inclusion Criteria:

- Male & female subjects ages 8-18 years (inclusive).

- Diagnostic Statistical Manual (DSM)-5 Autism Spectrum Disorder (ASD) diagnostic
criteria as established by clinical diagnostic interview

- At least moderate severity of social impairment as measured by a total raw score of
≥85 on the parent/guardian-completed Social Responsiveness Scale-Second Edition
(SRS-2)14 and a score of ≥4 on the clinician-administered Clinical Global
Impression-Severity scale (CGI-S)17.

Exclusion Criteria:

- IQ ≤70 based on the Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary
and Matrix Reasoning subtests

- Impaired communicative speech

- Subjects currently treated with the following medications (known to impact glutamate
levels): Lamotrigine, Amantadine, N-acetylcysteine, D-cycloserine

- Subjects treated with a psychotropic medication not listed above on a dose that has
not been stable for at least 4 weeks prior to study baseline.

- Co-administration of drugs that compete with memantine for renal elimination using the
same renal cationic system, including hydrochlorothiazide, triamterene, metformin,
cimetidine, ranitidine, quinidine, and nicotine

- Initiation of a new psychosocial intervention within 30 days prior to randomization.

- Subjects who are pregnant and/or nursing.

- Subjects with a history of non-febrile seizures without a clear and resolved etiology.

- Subjects with a history of or a current liver or kidney disease.

- Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.

- Subjects who meet on the Kiddie Schedule for Affective Disorders and Schizophrenia
(K-SADS-E) for alcohol or drug dependence or abuse. If the subject has a recent
history of substance abuse, there will be a two-week washout period before initiating
the trial as an added precaution. There are no known safety issues relating to
memantine and recent history of substance abuse.

- Serious, stable or unstable systemic illness including hepatic, renal,
gastroenterological, respiratory, cardiovascular (including ischemic heart disease),
endocrinologic, neurologic, immunologic, or hematologic disease.

- Subjects with severe hepatic impairment (LFTs > 3 times ULN).

- Subjects with genitourinary conditions that raise urine pH (e.g., renal tubular
acidosis, severe infection of the urinary tract).

- Known hypersensitivity to memantine.

- Severe allergies or multiple adverse drug reactions.

- A history of intolerance or adequate exposure to memantine, as determined by the
clinician.

- Investigator and his/her immediate family defined as the investigator's spouse,
parent, child, grandparent, or grandchild.